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Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Transcription Factor = TF, Growth Factor = GF
I.
Scribe: Sheena Harper
Proof: Sunita Jagani
Page 1 of 7
Overview of Neoplasia in Hematopoietic & Immune Systems [S1]:
a. The lecture is not meant for you to memorize the details.
b. He just wants to show that there’s a huge amount of detail on this topic in the medical literature.
c. What’s going to be on the test are very general concepts. The things you should focus on are the text slides
with bullet points. That’s generally where the test questions are going to come from. He just wants you to sit
back and try to get the idea of what we’re talking about and relay some ideas that are not conventional wisdom
in the field.
d. He is going to lay out what’s not the general information in the field, and to show that not everything is settled as
to what we think about cancer.
II. Neoplasia – Clonal Expansion due to Somatic mutations [S2]
a. A key concept is that neoplasia (opposed to in biology was called reactive hyperplasia) is a Heritable (genetic or
epigenetic) changes can be in germ line or acquired somatically it results in clonal formation.
b. Genetic change in the cells that is heritable. What genetic means in that sense is that it is a change in the
sequence or in the chromosome.
c. Epigenetic changes have to do with covalent changes at the histone or in the DNA itself that causes the pattern
of gene expression to be altered and that pattern is heritable from one generation to the next while it’s not a
change in the actual sequence. From the point of view of____(don’t know what he said here) selection… both
of those have the same consequence.
d. “Multiple Hit” concept
1. It’s seen that specific genetic changes are associated with specific forms of cancer; the developing
idea is a “Multiple Hit” phenomenon. You think of all the different genetic controls and all the
biochemistry that tackle the fundamental problem of biology: How do you go from a single cell, a
fertilized egg, to you? That is a seriously complicated biochemical problem. The machinery in
biochemical currents to allow this to happen is blindingly complex and can go bad.
2. Mutations happen. The rate of errors in DNA Polymerase is very low, but there’s 3 million base pairs
in the genome, so even if you make a mistake only now and then, there’s a lot of mistakes that can
happen. Sometimes those mistakes happen in ways that make those cells go weird. Most of the
time, the mutations that make that cell go weird result in the death of that cell, in the process of
evolution. Therefore it gets eliminated, but every now and then it hits a hot spot.
ii. Growth control pathways
1. Some of the classic hot spots are areas that control growth. If you get a mutation in a gene that
controls growth, it might start growing faster than it’s supposed to. That could be a precursor to a
neoplastic tumor.
iii. Genetic Stability (DNA repair, differentiation)
1. Another class is genetic stability. There are a lot of enzymes and machinery that are able to repair
critical mistakes that are made from the DNA’s copy. If you get mutations in those genes then you
don’t repair the error, some of them are going to land on a hot spot in that sort of repair zone cell,
and genes that are in that pathway are all called tumor suppressor genes. They will inhibit the
formation of the tumor if they’re expressed. What they’re doing is repairing genetic errors. If you
knock those out it leads to the greater frequency of genetic lesions.
iv. Blockade of Apoptosis
1. A third basic category is the blockade of apoptosis- particularly in the immune and dehydretic system
and a lot of the cells that we study in hematology, cells proliferate in the blood and they die on
escape. That’s the way neutrophils work for instance. Part of their normal activity is to die at the time
they’re supposed to.
a. It’s the same way with epithelial cells. Cells proliferate and as they go through their
differentiation, one of the differentiation signals is that they have to kill themselves. If you get
a defect in that kind of pathway, you are going to get an inflation of cells.
v. Tissue Invasion, metastasis, angiogenesis
1. Then the final pathway of cells has to do with division, invasion, metastasis, and angiogenesis. The
cell is able to digest its way through the basement membrane of the epithelium in particular is the
most common insidious situation.
2. Then you must express the right enzymes in order for it to bore a hole in what normally keeps the
basal cells where they’re supposed to be. If you express that enzyme then that’s going to allow the
cells to do that. Then they can get into the blood and the lymphatics, but they have to land
somewhere and set up shop and grow. Probably the vast majority of cells that get into the blood,
from say a breast cancer, land in a tissue that they can’t grow in, and they just die. Some of those
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 2 of 7
cells might have a genetic defect that allows those cells to grow in this site, and that one cell sets up
shop and makes a metastatic lesion, and it begins to grow.
vi. The way that cancer grows, there’s more than one thing that causes cancer. Not one from genetic
instability, one from apoptosis, and not one from metastasis. If an individual cell hit the jackpot and collects
mutations that occur in each of those different pathways, that’s what the development of carcinoma is.
Those are relatively limited set of genes that control the cells.
e. Retain many of the lineage specific programs of gene expression
1. There’s one other side, and so when an individual cell gets those mutations, it retains a lot of the
lineage specific patterns of gene expression. A liver cell still looks like a liver cell. Most of its
characteristics are those of a liver cell, so a liver cell carcinoma behaves differently than colon
carcinoma in a lot of different kind of ways, so the presence of these oncogenic mutations doesn’t
mean that the cell becomes an entirely different cell that forgot where it was. It retains those
features from before.
III. Two “Hit” Hypothesis (revised) [S3]
a. This is a diagram that says you can have these skips or mutations by several different mechanisms.
b. The initial two hit hypothesis suggests that there are two things that must occur for a cancer to form. He said
that it was multiple hits. He didn’t say how many hits there were, but there’s more than one.
c. Those hits could be epigenetic silencing, loss in heterozygosity- if you have two genes of a particular type and
one of them gets mutated, then it might not cause a problem if the other gene is still good, but loss in
heterozygosity means that the other gene gets damaged or is lost, and then you get the whole effect that the
other gene becomes the dominant trait.
IV. Neoplasic Progression [S4]
a. This is a classical view of neoplastic progression.
b. There are different ultimate carcinogens, primary carcinogens, things like viruses and radiation which will
damage DNA.
c. This starts a neoplastic process: called initiation in classical neoplastic study.
d. Those progress, and obviously cells that are nonviable die, but the cells that can grow have another mutation,
and that lesion progresses, and you get a benign change to one that is living, and then finally the definition of
cancer is the ability or likelihood of metastasis.
e. There’s a lot of things associated with this, but they progress one by one, and result in the ultimate full-blown
carcinoma.
V. Table [S5]
a. These are a list of genes that are inherited.
b. If you have one of these genes you already have a defect in column two, and therefore chances of getting three
numbers at random is greater than the chances of getting four independent. That’s what an increased
predisposition does.
c. A cancer predisposition gene just makes it more likely to have more than one hit since you already have one.
That doesn’t make you develop more mutations. All of your cells are still working. It doesn’t come together as a
whole intact genome that can cause uncontrolled abrasion. There’s a lot of them.
d. These are a sampling of genes that were known in 2004. The list is now longer.
e. People have tried to classify the pathway of what sequence cascade or what different means that cells use such
as different homoreceptors ect…There are multiple enzymes, hormones, cytokines in the environment that are
involved.
f. Any mutation in any part of that protein that’s involved can in the malfunctioning of that pathway.
g. It doesn’t really matter what the mutation is; It just matters that that pathway is affected, and this system goes
out of control.
h. There are a lot of genes that are inherited, and if you inherit that gene you’re more likely to develop that type of
cancer. BRACA-1 for instance has been associated with the development of breast cancer.
VI. Table [S6]
a. These genes are mutated somatically, but are not inherited in the mutated form, probably because they’d screw
up the germ cells.
b. There are a lot of different signal transduction type genes, growth factors, ect… that when they mutate they are
representative of one of those general categories of pathways that allows uncontrolled cell proliferation.
c. Again this is not an exhaustive list. This is just the ones that have been studied and well-characterized and we
know something about them. There are estimated to be 30,00 genes in the human genome, 3.3 million base
pairs, and that is a huge amount of information. This is just a scratch on the surface.
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 3 of 7
VII. Mechanisms of Translocation Oncogenesis with Transcription Factors [S7]
a. Another common mechanism besides a mutation is this kind of process.
b. This has been very well described in the hematopoietic system, in which you get a translocation between two
chromosomes, and you attach it at a promotor region or a regulatory region that would have been coding for a
tissue-specific gene.
c. For instance in the B cell system, the gene that controls immunoglobulin, which is always on in the B cells. B
cells are always making immunoglobulin. Only B cells make immunoglobulin.
d. The genetic machinery that drives this promotor is always on.
e. If it codes for a different gene product so that this promoter is in another gene that makes the cells grow or
blocks apoptosis, or some other defect that results in a neoplasia, then this translocation is associated with that
type of cancer.
i. There are certain fingerprints of the specific activity, and then a whole family of different target genes.
Some target genes are more preferentially picked out than others, and it’s not to say that the chromosomes
break in exactly that point, but there is definitely what are called recurrent translocations.
f. Sometimes you get a break in a gene that makes a binding protein. Say you have transcription factors that
controls yet another gene, and it binds the DNA in a particular site, which makes that particular site become
active. If you attach that binding protein to a control region, maybe that control region codes for other factors for
the promotor region that make that TF work, and now you get an aberrant pattern, and that fusion protein
generates a new biological behavior that in the end results in the outgrowth of a tumor.
VIII. Conserved cell death pathway [S8]
a. Here’s a well-described example where we have a conserved pathway of cell death or apoptosis. It’s conserved
because C. elegans, which is a little worm that’s about 1mm long, and it’s been extremely well-characterized
and has been longitudinally sectioned in its development.
b. C. elegans contains these genes that control cell death among different lineages.
c. In people there are genes that have a lot of sequence homology and work in roughly the same way, and they
constitually activate cell death via this biochemical pathway.
d. If you have a mutation in for instance leukemia where you get a new protein that comes in and binds to this
same region, but it doesn’t work in the same way, you get an inhibitory signal in this particular activity instead of
not working here it does, and it blocks the development of apoptosis. [17:32 End of Audio Part 1]
e. Then you get leukemia in cells that contain that particular mutation.
IX. Clonal Selection in Neoplasia [S9]
a. If you step back and think about it, you may have a bunch of normal stem cells, one gets this mutation- say a
GF control, and another gets an apoptosis defect, and that might cause attenuation, but then this daughter cell
gets a new mutation that really turns on growth, so the progeny of the first daughter cell doesn’t really
completely compete.
b. There’s heterogeneity during the development of the tumor. You get one defect, and that sets it up to potentially
have another one.
c. Another T factor that sets it up is what the amount of growth in the population is.
d. If cells are normally growing all the time they have more chances to make mutations. They have more chances
to have a hot spot be hit and then it proliferates.
e. Things like inflammation that cause a lot of proliferative activity in epithelium are predisposed to cancer- not
because they necessarily cause the mutation, but because the seabed of evolution is gross. If you’re in the
process of growth then you can be selected if you have a mutation that does that.
f. This process can take years to develop.
X. Stem Cell model of Neoplasia [S10]
a. There’s also the developing idea of a stem cell model of neoplasia, and what that means is sometimes you have
a translocation.
b. One of the daughter cells of that population may lose particular genetic information and become non-viable.
c. In the balance of what mix of some of this chromosome, some of that, a lot cells become aneuploidy, which
means that they don’t have the correct amount of DNA.
d. Some of the daughter cells become unstable and fall off, or they might differentiate and become end stage cells.
e. The idea is that not all of the cells of the tumor can regenerate the whole tumor.
f. ANL- a system which is studied in mice that is very well documented, and the basic kind of experiment is to take
the entire population of ANL cells and transfer them to an immunodeficient mouse, and count the frequency of
cells that you can generate tumors with. If that frequency is 100-fold less than the number of cells that you have
in the ANL, then that proves that the stem cell population is actually a minority of the total tumor.
g. SQ: How can we incorporate this information into Hematology?
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 4 of 7
h. Answer: Lots of hematology is also oncology. A lot of hematology is neoplastic lesions of the cells that are in
the blood: leukemias and lymphomas. Practicing hematologists probably spend 2/3 of their time dealing with
cancer. Dr. Pillion suggested he give some lectures about the immune system, but he talked to us about that
last year, so he thought we should talk about this subject.
i. If you step back and think about it, this is not that complex of an idea.
j. What if certain drugs that can kill tumor cells kill the tumor cells that really aren’t the stem cells, and we select
those drugs to be good for that tumor because they reduce the bulk of the tumor, but it doesn’t really kill the
stem cells. Therefore, that’s really not going to be an effective treatment. It shows activity when what you
measure is killing the bulk of the cell.
k. Unless you treat the stem cell you’re not going to kill the tumor. Therefore we may have a problem.
l. The reason that certain therapies don’t work or people have recurrence of tumors is that the treatment may not
kill the stem cells.
XI. Tumor Heterogeneity [S11]
a. This is kind of a new concept. Then to combine these ideas with the development of the tumor as well as this
stem cell idea of heterogeneity, a tumor itself could be seen as sort of a competing set of individual cells. The
reason that that’s important is if you apply particular drugs that block say topoisomerase- the thing that controls
how the synthesize is being made and rearranging the structure of the chromosomes.
b. That might cause selection of the mutation in the binding proteins that allow the escape from that particular
change. Because all of the cells are competing one cell that had that particular defect could grow out, and you
get the development of resistance to chemotheraputic agent because that’s a selective trait. Just like we have
bacteria that develop resistance to antibiotic therapy.
II. Diagnostic Categories vs Mechanisms [S12]
a. There are two places at least where these concepts have sort of unexpected consequences.
b. One is our nomenclature system. To step back and say what’s the purpose of having a diagnostic entity.
c. Purpose of Diagnostic Entities
i. Establish Therapeutic alternatives The key point is that you establish what the therapy is going to be. If you put a particular disease
syndrome in a box with a name, they you can develop consistent strategies to treat that name.
 For that to be useful we want a mapping of the diagnostic category and a treatment plan.
 If we find out that there are two different diseases: ones that look the same, but you treat them
differently, you want to have different names for those two so that you can treat them differently.
ii. Implications about Prognosis What’s going to happen to this disease over the course if it’s not treated?
 That really doesn’t have anything to do with rapidness?
 We don’t have to know the mechanism of the disease, but that may help.
 Then you get sort of history coming along.
d. Implicit concept that a name means a Category with qualitative distinctions.
i. The concept that a name implies a category that is an isolated entity as opposed to seeing what is going on
as a mechanistic process. What do you do when you get confusion not sort of going on, but with the
conventional names of things?
e. Mechanistic understanding is preferred, but has limitations
i. Mechanisms often unknown (especially historically when nomenclature established)
 Mechanistic understanding is sort of in our culture to be sort of private practice scientific-based
medicine.
 You are learning a lot of scientific stuff, and you’re probably sitting there wondering why do I need to
know all of this right now. Part of the idea is that if we understand what is going on, we can better
incorporate change. We can incorporate new information into a coherent framework and understand
what’s going on and separate that from the bullshit that some drug company rep will give you
involving other kinds of information.
ii. Basing the nomenclature on a mechanistic process is often a problem because the mechanism is not
known where nomenclature is historic.
f. Complexity of related mechanisms (lump/split)
i. Furthermore you have the complexity of different mechanisms.
g. Evolution of understanding vs Nomenclature
i. Where he is going here is to talk about how do you name things?
III. Heterogeneity of tumors and Screening to detect early lesions [S13]
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 5 of 7
a. Recently, in fact this week in he New York Times, there was an article about challenging the convention wisdom
of screening for cancer.
b. Conventional Wisdom has long held that finding cancer early leads to better “cure” rate.
i. The conventional wisdom is that the earlier we find a cancer, then that leads to a better cure rate because
we stopped it earlier, and that makes a certain amount of sense, but there are some problems.
c. For Breast and Prostate Cancer, screening over last 20 years has:
i. Increased incidence of early stage Cancer detection
ii. Not changed incidence of late stage Cancer
iii. Not changed overall Cancer death rate
 For breast and prostate cancers, which are common cancers. Women have almost a 10% chance
over the course of their lifetime to develop breast cancer if they live to be 85, which a lot of people
live that long now. This is not a tiny possibility.
 Prostate cancer is fairly common. In studies looking at old men at autopsies, the calculation is that
you have 100% incidence of prostate cancer by the time you’re 95 years old. Maybe people die
before that of MI or something like that, but it’s a very high incidence kind of cancer, and you can
screen for that with prostate specific antigens and proteins in the blood made by prostate cells
specifically.
 A program of screening over the years has increased the incidence of early stage cancer detection.
 Before screening for death, there were fewer absolute numbers of cancer diagnosed for the same
number of people.
 When you start screening, sure enough, you find more cancers, but the incidence of late stage
cancer and the death rate from cancer is totally the same.
 Over time if you catch it earlier, if you wait a while you think that it will result in a lower death rate
because you caught the cancer earlier, but that’s not what the data has.
d. Screening for colon and cervical cancer has decreased death rate.
i. On the other hand screening for colon and cervical cancer by colonoscopy and a pap smear, that actually
has resulted in decreased total death rate after the screening program was there.
ii. The death rate in the late stage cancers are present in the same incidence even though we are finding
more people with early stage cancer.
e. SQ: Could one reason for this be that cancer is changing?
i. Answer: You could make the argument that … I couldn’t really hear all of his answer…There is not really an
answer for this question. There is a concern that our convention wisdom could not be as clear as we
originally thought. One possibility that you could argue along those lines is that we’re exposed to more
carcinogens, but this really hasn’t changed much compared to 20 years ago, so it’s hard to really sustain
that kind of reasoning.
 Another possibility is that what we’re calling cancer is not quite tight anymore. If you go in and look
for symptoms, you find genetic lesions behind cells that are on the verge of cancer, but they really
would never develop into a real cancer, but the way we detect cancer, we call it cancer. It’s not
cancer in the sense that it’s very likely to metastasize.
 How do we know what cancer is? We find things that have in the past been associated with
metastasis, but the pattern of gene expression and what we think these genes are is really
complicated. We’re calling things cancer that really shouldn’t be. That’s the problem of lumping
everything into this one name, which is just not sufficient to handle the complexity of this. We have
to learn to take that apart and say this is a cancer that looks like cancer below the basement
membrane in the prostate, but it’s probably not going to kill you so just sit tight. That’s hard to do.
 People that are told they have cancer want surgery to take it out. The problem is that if you take out
the prostate, most men become impotent, there’s a lot of urinary problems and leakage. It’s not a
benign procedure. If you weren’t going to have a problem anyway is it really worthwhile?
 Another example is that radiation for breast cancer is not a fun thing. If you don’t need to do that it
would be nice to be able to tell which ones are really bad as opposed to which ones will be ok. We
have gotten too good at diagnosis but not good enough. That’s where the field is at this particular
time.
f. Does sensitive screening pick up lesions that would not really progress to late stage lesions?
i. That’s the suggestion that’s being made. It’s a call to the research agenda and also a cautionary tale about
how to practice medicine.
ii. There was a big study done on prostate cancer that came out a few months ago comparing two studies:
one done in Europe and one done in the US on the ability of screening for prostate cancer to affect death.
There were 80,000 patients in this study, so it was very sensitive to detect very minor differences. The
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 6 of 7
European study showed that only 1 out of 50 of the subjects that were screened were saved from death
from treatment of prostate cancer. In the European study the control group did what they were supposed to
and didn’t get screened. In the US study as many as 60% of the control group didn’t do what they were
supposed to and got screened and continued with treatment. Different styles of the way of practice
determine what we can learn about this.
iii. There was a SQ here, but it was hard to hear the question and answer, and it was really just clarifying that
in these cases, the benign cancers weren’t treated. Only the malignant ones where, but he’s saying what if
what they called malignant was not actually malignant, and therefore really didn’t need treatment. It’s hard
to determine the future of the prognosis, so they treat these things, but what if they really didn’t need to be
treated after all?
iv. Because we’re aggressive about doing something, it messes up our goal to really understand what we’re
doing. Who is going to agree to not be treated for cancer? That’s a tough study to do.
v. What do we do with lymphomas because lymphocytes are normally metastatic?
vi. There was a clicker question here, which we aren’t supposed to scribe, so I’m not going to include the
choices for the question, but I will include his conclusion and explanation of his point here.
vii. The general theory for determining if something is benign of malignant is the idea that malignant tumors
have the ability to metastasize. How do you handle the problem the malignancy of a cell that normally
goes around the body all the time and is therefore metastatic? How do you make that distinction between
benign and malignant in that circumstance?
viii. Bone marrow infiltration is in equilibrium with the blood, so that’s not an option for classification of
lymphomas.
ix. Based on this classification of malignancy, there is no such thing as a benign tumor of lymphocytes. This
really isn’t reasonable on a mechanistic standpoint, but that’s because we’re trapped by history. We didn’t
understand that when the nomenclature of these things got developed. Everything that’s a neoplastic
lymphocyte is called a lymphoma or leukemia. We don’t allow for a possibility that there’s a benign
condition. He thinks there are people that have that benign condition, but we name it metastatic based on
the nomenclature.
IV. Nomenclature based on Stage of Normal Differentiation [S14]
a. We name things based on the derivation of the cells- not on the mechanism.
b. THE AUDIO CUT OUT HERE, AND I HAVE NO MORE AUDIO FOR THE REST OF THE LECTURE, SO THIS
IS THE NOTES I TOOK FROM CLASS. EVERYTHING HERE MAY NOT BE CORRECT. I JUST TYPED UP
WHAT I CAUGHT FROM CLASS. IF ANYONE HAS BETTER NOTES THEY WOULD LIKE TO SHARE OR
ADD IN HERE FEEL FREE. IF NOT, I GUESS THIS IS ALL WE HAVE FOR THE SECOND HALF OF THE
LECTURE.
c. They’re named based on what cell they’re likely to be of origin.
d. This cell changed from being a normal cell to a cancerous cell.
e. This is a scheme of B cell development
V.
Tables [S15]
a. These are the different classes of lymphomas.
b. There’s a lot of different surface markers that you can detect from cytogenetic abnormalities.
VI. WORLD HEALTH ORGANIZATION CLASSIFICATION OF THE TUMORS OF THE HEMATOPOIETIC AND
LYMPHOID TISSUES - 2008 [S16]
VII. Article [S17]
a. This is a study that did a genome wide mutation study. They looked at 232 patients with acute lymphoblastic
leukemia.
VIII. Mutations in PAX5 in B-ALL [S18]
a. They found that 30% of the patients had mutations in the PAX5 gene that determines B- cell development.
b. Out of 232, only 2 had the same mutation.
IX. Gene Expression Analysis of DLBCL [S19]
a. This is a gene expression array.
b. They came down to two different kinds of diffuse pre-cell lymphoma.
c. It’s not clear that that’s completely stable.
X. Article [S20]
a.
b.
XI. Three Pathways with Mutations in Glioblastoma [S21]
Heme/Endo: 11:00-12:00
Scribe: Sheena Harper
Friday, October 23, 2009
Proof: Sunita Jagani
Dr. Bucy
Overview of Neoplasia in Hematopoietic & Immune Systems
Page 7 of 7
a.
b.
XII. Graphical representation of the interactions and networking of the 213 glioma genes [S22]
a. They tried to correlate what genes were involved and what pathways were involved.
b. There’s a blizzard of different genetic defects.
XIII. Article [S23]
a. They found a lot of stuff all the time.
b. Almost every time the individuals had a different mutation.
XIV.
Diagrams of Mutation in Selected Receptor Families [S24]
XV. Significant Muatated pathways in lung adenocarcinoma [S25]
XVI.
Core Signaling Pathways [S26]
XVII.
Mutations in Pancreatic Cancer [S27]
a. There are 50 different mutations involved.
XVIII. Table [S28]
a. Essentially all of the cancers had multiple pathways that were affected.
The allure of “Personalized Medicine” [S29]
a. They sequenced the entire genome of an individual to determine the entire base pair changes in an individual. It
cost over a million dollars.
XX. Graphs [S30]
a. This individual had 1.7 million different base pair changes.
b. They found 700,000 different sequences between that person’s tumor and their own genes.
c. You must sequence everyone to determine the best treatment, but that’s impossible.
XIX.
XXI.
“Personalized Medicine in Oncology” [S31]
a. Molecular Analysis as route to Mechanisms
i. Fundamental understanding of differentiation and neoplasia
ii. Development of molecular targets for Drug Development
b. Diagnostic Utility of detailed molecular Phenotype
i. Selection of Targeted Therapy
ii. Impulse to “Complete” Work-up
iii. Cost of analysis versus therapeutic benefit
iv. Growing Financial Constraints
[ End 22:51 of second audio]